Abstract 4190: Patient-derived xenograft (PDX) models with differential HER2 expression for preclinical evaluation of HER2-targeted therapies

Abstract

Abstract Human epidermal growth factor receptor 2 (HER2) is a critical therapeutic target in gastric cancer. However, the varying expression levels of HER2 in patients present a significant challenge in selecting the appropriate HER2-targeted therapies. Patient-derived xenograft (PDX) models offer a valuable tool to address this clinical concern. We established a panel of PDX models derived from gastric cancer patients, each representing a distinct range of HER2 expression levels. These models were subsequently treated with HER2-targeted drugs, including Trastuzumab (Herceptin), Margetuximab, and Enhertu. Our results demonstrated differential drug responses corresponding to the varying HER2 expression levels in the PDX samples. Trastuzumab, Margetuximab, and Enhertu exhibited distinct efficacies across the HER2 expression spectrum. This underscores the significance of selecting the right therapeutic approach based on the HER2 status of individual patient. Our collection of PDX models with differential HER2 expression levels provides a robust platform for preclinical evaluation of HER2-targeted therapies. This approach not only addresses the clinical challenge of HER2 heterogeneity but also facilitates a more personalized and effective treatment strategy for gastric cancer patients. Citation Format: Xiaoliu Yang, Shiying Guo, Huiyi Wang, Xu Su, Jing Zhao, Xiang Gao, Cunxiang Ju. Patient-derived xenograft (PDX) models with differential HER2 expression for preclinical evaluation of HER2-targeted therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4190.